The mechanism by which demyelination is caused by inflammatory cells infiltrating the central and peripheral nervous system will be explored with emphasis on the role of proteolytic enzymes in initiating myelin degradation. Lymphocytes from lymph nodes of rats with acute EAE and macrophages from peritoneal washings of rats will be incubated with purified myelin basic protein, and peptide maps and amino acid end groups of the hydrolysis products will be identified. Since myelin basic protein may be the most vulnerable protein in CNS myelin, its pattern of breakdown by these two kinds of cells will identify possible hydrolytic pathways occurring in the CNS during cell-mediated demyelination. Purified CNS and PNS myelin will be incubated with purified enzymes including acid proteinase, elastase, and collagenase, as well as lymphocytes and macrophages to determine the extent to which the different myelin proteins are vulnerable to hydrolysis by these enzymes and cells. Special attention will be directed toward the possibility that PO, the major glycoprotein in PNS myelin, may be a precursor to certain other glycoproteins. Synthesis of PNS myelin during the initial myelination and during demyelinative episodes will be investigated in vitro using sciatic nerves and spinal roots incubated with radioactive precursors. Metabolic correlates of myelin damage will be studied in spinal roots of rats with EAN, in sciatic nerves treated with lysolecithin, in sciatic nerves of young rats treated with 6-aminonicotinamide, and sciatic nerves of adult rats treated with misonidazole.